Eczematous dermatitis is a characteristic inflammatory response of the skin due to both endogenous and exogenous factors. Eczematous dermatitis is sufficiently serious to account for the highest incidence of skin disease, being response for incalculable loss of time and productivity in industry. Approximately one-third of all patients in the United States seen by dermatologists have eczema.
In particular, classic delayed-type hypersensitivity and allergic contact dermatitis represent common clinical problems. The potential contact sensitizing antigens to which humans are exposed are multitudinous and include drugs, dyes, plant oleo resins, preservatives, and metals. The five most common contact sensitizing agents encountered in clinical practice are Rhus species of plants (poison ivy, oak, or sumac), paraphenylenediamine, nickel compounds, rubber compounds, and the dichromates. They can lead to delayed hypersensitivity responses, which may represent significant medical problems. Thus a great deal of study has focused on pharmacological ways to modulate this type of immune response.
Delayed-type hypersensitivity (DTH) is a T-cell dependent immune phenomenon manifested by an inflammatory reaction at the site of antigen deposition, usually the skin, that reaches its peak intensity 24 to 48 hours after challenge by the antigen. Contact sensitivity (CS), a form of DTH, is observed by sensitizing animals to antigen through cutaneous exposure to highly chemically reactive compounds such as trinitrochlorobenzene (TNCB) or dinitrofluorobenzene (DNFB). Animals are subsequently challenged on the skin or on the pinna of one ear 4 to 7 days after sensitization with the contact sensitizer (allergen), and an inflammatory response is observed 24 to 48 hours after challenge. In mice, antigen can be deposited in the pinna or on the foot pad and the swelling determined with callipers or an engineer's micrometer. Swelling in mice sensitized with irrevelant antigen and challenged in the foot pad with the same antigen as the experimental group provides the control for non-specific swelling.
The immune lymphocytes mediating DTH probably encounter antigen at or close to the site of antigen deposition. Studies indicate that Ia-bearing Antibody Presenting Cells take up antigen and "present" it to T-cell precursors to prime them resulting in sensitization. In sensitized animals challenged with allergen, a similar interaction seems to occur between antigen-bearing Antibody Presenting Cells and primed T-cells in order to activate the T-cells. After activation, T-cells secrete a number of lymphokines responsible for attracting mononuclear cells to the inflammatory site and activating them to evolve non-specific tissue destruction. In the case of contact allergic dermatitis, the Antigen Presenting Cell function is apparently supplied by epidermal Langerhans cells.
The simplest treatment of allergic contact dermatitis is avoidance of exposure to an identified allergen, but avoiding known allergens may prove difficult. For example, common sensitizers such benzocaine are employed in a variety of topical medications such as sunburn preparations and antiseptic creams. Unwitting exposure to a known allergen such as poison ivy can occur through contact with the smoke of burning leaves. In addition, the patient may exacerbate an allergic contact dermatitis by exposure to cross-reacting chemical compounds that are similar to the allergen by which the patient was originally sensitized.
Symptomatic treatment usually consists of the application of topical corticosteroids. Prolonged topical use of corticosteriods can produce undesirable side effects such as atrophy of the skin and systemic absorption of the corticosteriods. Oral or parenteral corticosteriods may be needed temporarily in severe cases, but long term therapy with exogenous corticosteriods can produce Cushing's syndrome. The decreased DTH seen in mammals exposed to steroids might be due to the lympholytic function of these agents. In addition it has recently been observed that glucocorticosteriods applied topically or administered systemically seem to lead to a decrease in the density of epidermal Langerhans cells, which are critically important in the presentation of antigen in contact sensitivity.
Another potential approach to treatment of DTH involves systemically depleting Antigen Presenting Cells by ultraviolet radiation. It has been shown in vivo exposure of mice to UV irradiation leads to impaired antigen presentation by Antigen Presenting Cells and to a systemic decrease in the number of Ia-bearing Antigen Presenting Cells. Many Ia-bearing Langerhans cells, which are known to be important in the presentation of skin contactants to immune T-cells, also disappear from the skin. When such UV-irradiated mice are contact sensitized or immunized subcutaneously with hapten-coupled cells, they are not primed for DTH responses; instead they develop antigen-specific suppressor T-cells. Thus one can selectively modulate activation of T-cells by preventing presentation of ligand by Antigen Presenting Cells. It has not been proven that an identical phenomenon occurs in human beings exposed to UV irradiation.